Document Type

Article

Publication Date

4-19-2022

Publication Title

Cell Rep

Keywords

JGM, RNA, Long Noncoding, Tumor Suppressor Protein p53

JAX Source

Cell Rep 2022 Apr 19;39(3):110687

Volume

39

Issue

3

First Page

110687

Last Page

110687

ISSN

2211-1247

PMID

35443176

DOI

https://doi.org/10.1016/j.celrep.2022.110687

Abstract

The p53-induced long noncoding RNA (lncRNA) lincRNA-p21 is proposed to act in cis to promote p53-dependent expression of the neighboring cell cycle gene, Cdkn1a/p21. The molecular mechanism through which the transcribed lincRNA-p21 regulatory locus activates p21 expression remains poorly understood. To elucidate the functional elements of cis-regulation, we generate a series of genetic models that disrupt DNA regulatory elements, the transcription of lincRNA-p21, or the accumulation of mature lincRNA-p21. Unexpectedly, we determine that full-length transcription, splicing, and accumulation of lincRNA-p21 are dispensable for the chromatin organization of the locus and for cis-regulation. Instead, we find that production of lincRNA-p21 through conserved regions in exon 1 of lincRNA-p21 promotes cis-activation. These findings demonstrate that the activation of nascent transcription from this lncRNA locus, but not the generation or accumulation of a mature lncRNA transcript, is necessary to enact local gene expression control.

Comments

This is an open access article under the CC BY-NC-ND license.

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